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===DNA damage and repair=== DNA damages present in spermatozoa in the period after [[meiosis]] but before [[Human fertilization|fertilization]] may be repaired in the fertilized egg, but if not repaired, can have serious deleterious effects on fertility and the developing embryo. Human spermatozoa are particularly vulnerable to free radical attack and the generation of oxidative DNA damage.<ref name="pmid26178844">{{cite book |doi=10.1007/978-3-319-18881-2_2 |pmid=26178844 |chapter=Damage to Sperm DNA Mediated by Reactive Oxygen Species: Its Impact on Human Reproduction and the Health Trajectory of Offspring |title=The Male Role in Pregnancy Loss and Embryo Implantation Failure |volume=868 |pages=23–47 |series=Advances in Experimental Medicine and Biology |year=2015 |last1=Gavriliouk |first1=Dan |last2=Aitken |first2=Robert John |isbn=978-3-319-18880-5 }}</ref><ref>{{cite journal | last1 = Lozano | first1 = G.M. | last2 = Bejarano | first2 = I. | last3 = Espino | first3 = J. | last4 = González | first4 = D. | last5 = Ortiz | first5 = A. | last6 = García | first6 = J.F. | last7 = Rodríguez | first7 = A.B. | last8 = Pariente | first8 = J.A. | year = 2009 | title = Density gradient capacitation is the most suitable method to improve fertilization and to reduce DNA fragmentation positive spermatozoa of infertile men | url = https://www.researchgate.net/publication/259983025 | journal = Anatolian Journal of Obstetrics & Gynecology | volume = 3 | issue = 1 | pages = 1–7 | access-date = 2016-03-08 | archive-date = 2022-04-30 | archive-url = https://web.archive.org/web/20220430005522/https://www.researchgate.net/publication/259983025_Density_gradient_capacitation_is_the_most_suitable_method_to_improve_fertilization_and_to_reduce_DNA_fragmentation_positive_spermatozoa_of_infertile_men | url-status = live }}</ref> (see e.g. [[8-Oxo-2'-deoxyguanosine]]) Exposure of males to certain lifestyle, environmental or occupational hazards may increase the risk of [[Aneuploidy|aneuploid]] spermatozoa.<ref>{{cite journal |vauthors=Templado C, Uroz L, Estop A |title=New insights on the origin and relevance of aneuploidy in human spermatozoa |journal=Molecular Human Reproduction|volume=19 |issue=10 |pages=634–43 |year=2013 |pmid=23720770 |doi=10.1093/molehr/gat039 |doi-access= }}</ref> In particular, risk of aneuploidy is increased by tobacco smoking,<ref name="pmid11468778">{{cite journal |vauthors=Shi Q, Ko E, Barclay L, Hoang T, Rademaker A, Martin R |title=Cigarette smoking and aneuploidy in human sperm |journal=Molecular Reproduction and Development |volume=59 |issue=4 |pages=417–21 |year=2001 |pmid=11468778 |doi=10.1002/mrd.1048 |s2cid=35230655 }}</ref><ref name="pmid9797104">{{cite journal |vauthors=Rubes J, Lowe X, Moore D, Perreault S, Slott V, Evenson D, Selevan SG, Wyrobek AJ |title=Smoking cigarettes is associated with increased sperm disomy in teenage men |journal=Fertility and Sterility |volume=70 |issue=4 |pages=715–23 |year=1998 |pmid=9797104 |doi= 10.1016/S0015-0282(98)00261-1|doi-access=free }}</ref> and occupational exposure to benzene,<ref name="pmid20418200">{{cite journal |vauthors=Xing C, Marchetti F, Li G, Weldon RH, Kurtovich E, Young S, Schmid TE, Zhang L, Rappaport S, Waidyanatha S, Wyrobek AJ, Eskenazi B |title=Benzene exposure near the U.S. permissible limit is associated with sperm aneuploidy |journal=Environmental Health Perspectives |volume=118 |issue=6 |pages=833–9 |year=2010 |pmid=20418200 |pmc=2898861 |doi=10.1289/ehp.0901531 }}</ref> insecticides,<ref name="pmid15363581">{{cite journal |vauthors=Xia Y, Bian Q, Xu L, Cheng S, Song L, Liu J, Wu W, Wang S, Wang X |title=Genotoxic effects on human spermatozoa among pesticide factory workers exposed to fenvalerate |journal=Toxicology |volume=203 |issue=1–3 |pages=49–60 |year=2004 |pmid=15363581 |doi=10.1016/j.tox.2004.05.018 |bibcode=2004Toxgy.203...49X |s2cid=36073841 }}</ref><ref name="pmid15615886">{{cite journal |vauthors=Xia Y, Cheng S, Bian Q, Xu L, Collins MD, Chang HC, Song L, Liu J, Wang S, Wang X |title=Genotoxic effects on spermatozoa of carbaryl-exposed workers |journal=Toxicological Sciences |volume=85 |issue=1 |pages=615–23 |year=2005 |pmid=15615886 |doi=10.1093/toxsci/kfi066 |doi-access=free }}</ref> and perfluorinated compounds.<ref name="pmid25382683">{{cite journal |vauthors=Governini L, Guerranti C, De Leo V, Boschi L, Luddi A, Gori M, Orvieto R, Piomboni P |title=Chromosomal aneuploidies and DNA fragmentation of human spermatozoa from patients exposed to perfluorinated compounds |journal=Andrologia |volume= 47|issue= 9|pages= 1012–9|year=2014 |pmid=25382683 |doi=10.1111/and.12371 |hdl=11365/982323 |s2cid=13484513 |doi-access=free }}</ref> Increased aneuploidy of spermatozoa often occurs in association with increased DNA damage. [[DNA fragmentation]] and increased in situ DNA susceptibility to denaturation, the features similar to these seen during [[apoptosis]] of somatic cells, characterize abnormal spermatozoa in cases of [[male infertility]].<ref>{{cite journal | last1 = Gorczyca | first1 = W | last2 = Traganos | first2 = F | last3 = Jesionowska | first3 = H | last4 = Darzynkiewicz | first4 = Z | year = 1993 | title = Presence of DNA strand breaks and increased sensitivity of DNA in situ to denaturation in abnormal human sperm cells. Analogy to apoptosis of somatic cells | journal = Exp Cell Res | volume = 207 | issue = 1| pages = 202–205 | doi = 10.1006/excr.1993.1182 | pmid = 8391465 }}</ref><ref>{{cite journal | last1 = Evenson | first1 = DP | last2 = Darzynkiewicz | first2 = Z | last3 = Melamed | first3 = MR | year = 1980 | title = Relation of mammalian sperm chromatin heterogeneity to fertility | journal = Science | volume = 210 | issue = 4474| pages = 1131–1133 | pmid = 7444440 | doi=10.1126/science.7444440| bibcode = 1980Sci...210.1131E }}</ref> Although [[DNA repair]] has long been considered impossible in human spermatozoa due to the high level of DNA compaction in these cells, human spermatozoa possess a truncated [[base excision repair]] pathway that is mediated by [[oxoguanine glycosylase|8-oxoguanine DNA glycosylase 1 (OGG1)]].<ref name = Smith2013>{{cite journal |vauthors=Smith TB, Dun MD, Smith ND, Curry BJ, Connaughton HS, Aitken RJ |title=The presence of a truncated base excision repair pathway in human spermatozoa that is mediated by OGG1 |journal=J Cell Sci |volume=126 |issue=Pt 6 |pages=1488–97 |date=March 2013 |pmid=23378024 |doi=10.1242/jcs.121657 |url=}}</ref> Thus mature spermatozoa appear to have a limited capacity to mount a DNA repair response to [[oxidative stress]].<ref name = Smith2013/>
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